Sufentanil is a piperidine derivative and is one member of a series of potent fentanyl analogues. Other 4-anilido-piperidines in this series are remifentanil, carfentanil and alfentanil. In general, these materials are characterized by a high analgesic potency, a short duration of action and a relatively good overall safety margin during surgical anesthesia.
Sufentanil, in particular, is considered a powerful analgesic with an excellent safety margin as compared to other narcotic agents. Sufentanil has a high selectivity and affinity (approximately 10 times greater than fentanyl) for “mu” opiate receptors. Unlike fentanyl or morphine, sufentanil produces anesthesia with minimal side-effects. Sufentanil, when used in high doses with 100% oxygen in patients undergoing major surgical procedures has shown excellent cardiovascular stability, maintaining cardiac output and myocardial oxygen balance with minimal changes in heart rate.
Because of its low cardiovascular toxicity, sufentanil has utility as a total intravenous anesthetic for major surgical procedures and finds particular utility for open heart surgery and major operations in patients with severe cardiovascular compromise.
The chemical name for sufentanil is N-[4-(methoxymethyl)-1[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylpropanamide. Sufentanil citrate is a white crystalline powder (molecular weight=578.68) that is very soluble in water and most common organic solvents.
Methods of synthesizing sufentanil and related piperidine derivatives are described in the following references: U.S. Pat. Nos. 3,998,834, 4,179,569, 5,489,689 and WO 2008/005423; each of which is incorporated herein by reference in its entirety. There remains a need in the art for improved processes for producing such piperidine derivatives including sufentanil.